System and method for ultrasonic harmonic imaging for therapy guidance and monitoring

ABSTRACT

An ultrasound system is provided which includes a therapy ultrasound transducer and a diagnostic ultrasound transducer and operates in accordance with a method to direct the application of the therapy ultrasound. The method includes operating the diagnostic ultrasound transducer to acquire a first ultrasound image; simultaneously operating the diagnostic ultrasound transducer and therapy ultrasound transducer for a second interval to acquire a second ultrasound image; and determining a difference in the first and second images indicative of the pattern of the therapy ultrasound transducer signal. The difference in the images, which result from enhanced non-linearities and propagation distortions induced by the high intensity therapy ultrasound, can be obtained by subtracting the two images. A method is also provided for monitoring the progress of high intensity therapy ultrasound which evaluates transient changes due to in-situ heating as well as permanent changes which result from cell microstructure alteration.

[0001] This application is a divisional application of copending U.S.patent application Ser. No. 10/350,994 entitled SYSTEM AND METHOD FORULTRASONIC HARMONIC IMAGING FOR THERAPY GUIDANCE AND MONITORING, whichis a divisional application of copending U.S. patent application Ser.No. 09/634,272 entitled SYSTEM AND METHOD FOR ULTRASONIC HARMONICIMAGING FOR THERAPY GUIDANCE AND MONITORING, which was filed on Aug. 8,2000 and claims the benefit of U.S. Provisional Application Serial No.60/147,769, filed on Aug. 9, 1999.

FIELD OF THE INVENTION

[0002] The present invention relates generally to ultrasonic imaging andmore particularly relates to the use of harmonic imaging to guide andmonitor the application of therapeutic ultrasound.

BACKGROUND OF THE INVENTION

[0003] It is known in the art of medical imaging and therapy thatultrasonic energy can be used for both diagnostic purposes andtherapeutic purposes. For example, high-intensity focused ultrasound(HIFU) beams can be used to treat tumors by causing local focaltemperature increases that cause cell necrosis. In using HIFU, thelocation of the focused ultrasound beam must be determined to place thebeams focal point on the tissue (tumor) which is targeted for therapy.In addition, it is desirable to sense and monitor changes which areinduced by the HIFU beam within the exposed tissue.

[0004] It is known that non-linear propagation occurs in a medium, suchas tissue, which is exposed to intense ultrasound pressure, such as thatwhich occurs from a HIFU beam. The HIFU beam is a high intensitypressure wave which alternately compresses and relaxes the tissue duringa signal cycle. As a beam propagates, regions of compression can disturblocal propagation speeds and result in regions of increased speeds incompression segments and decreased propagation speeds in rarefactionsegments of the wave. This effect locally increases with increasing peakpressure values and also exhibits a cumulative nature, i.e., becomingmore prominent as an intense beam propagates further into a medium. Thistends to distort the propagating pressure wave and enhancenon-linearities in the echo signal. This results in a generation ofhigher-order harmonics and mixing products in a propagating ultrasoundsignal. This process is altered, however, by attenuation losses intissue, which typically increase with increasing frequency.

[0005] The use of harmonic imaging in diagnostic imaging is also knownin the prior art. However, such systems have been generally used toimage non-linear scattering from small, gas-filled contrast agentparticles. An example of this can be found in applicants' copendingapplication, Ser. No. 09/318,882, filed on May 26, 1999 and entitled,“Ultrasonic Systems and Methods for Fluid Perfusion and Flow RateMeasurement,” which is hereby incorporated by reference. There are alsoreports that different tissues exhibit different non-linear propertiesthat can be observed in second-harmonic images if the peak pressures ofthe launched pulse are sufficiently large.

[0006] Although harmonic imaging techniques have been evaluated and thenon-linear properties of tissues have been observed in the past, theseeffects have not been used in an advantageous matter to guide andmonitor the progress of therapeutic ultrasound.

SUMMARY OF THE INVENTION

[0007] It is an object of the present invention to provide a system andmethod for aiming a therapy ultrasound beam.

[0008] It is a further object of the present invention to provide asystem and method for monitoring the application of a therapy ultrasoundbeam using harmonic imaging.

[0009] It is another object of the present invention to provide a systemand method for detecting thermal lesions resulting from the applicationof therapeutic ultrasound and determining the position of such lesionsusing ultrasound harmonic imaging.

[0010] A present method is used for aiming or directing a focusedultrasonic therapy beam. The method begins by acquiring a first imagescan using a first frequency ultrasound signal. A second image scan isthen acquired using the first frequency ultrasound signal in thepresence of a therapy beam ultrasound signal. Difference properties inthe first and second image scans are then identified to determine wherethe focused ultrasonic therapy beam is currently directed. Thedifference properties can be obtained by generating a difference imagefrom the first image and second image scans. The difference image canthen be superimposed on the first image scan and displayed to illustratethe presence of the focused ultrasonic therapy beam.

[0011] Preferably, the method described is used in conjunction with anultrasound system which includes a diagnostic ultrasound transducer anda high intensity focused ultrasound therapy transducer which arearranged in a collinear fashion. It is also preferred that the imagescans take the form of non-linearity imaging scans, such as harmonicimaging or pulse inversion imaging.

[0012] A further method is provided for operating an ultrasound therapysystem having a therapy ultrasound transducer and a diagnosticultrasound transducer to direct the application of the therapyultrasound. The method includes operating the diagnostic ultrasoundtransducer for a first interval to acquire a first ultrasound imagescan; simultaneously operating the diagnostic ultrasound transducer andtherapy ultrasound transducer for a second interval to acquire a secondultrasound image scan; and determining a difference in the first andsecond image scans indicative of the pattern of the therapy ultrasoundtransducer signal.

[0013] A method of monitoring ultrasound therapy is also provided. Thismethod begins by acquiring a first ultrasound image (baseline) of aregion subjected to therapy. High intensity ultrasound is then appliedto the region for a first time period. A second ultrasound image of theregion is then acquired after the first time period. An aggregateinduced effect can be determined based on the first and second imagescans. The high intensity ultrasound can then be discontinued for asecond time period and a third ultrasound image is then acquired.Transient changes due to in-situ heating in the region and permanentchanges due to alteration in tissue microstructure in the region canthen be determined.

[0014] Generally, the first time period is selected to be long enoughsuch that the applied high intensity ultrasound has a therapeuticeffect. The second time period is selected to allow cooling of theregion undergoing high intensity ultrasound therapy.

BRIEF DESCRIPTION OF THE DRAWING

[0015] Further objects, features and advantages of the invention willbecome apparent from the following detailed description taken inconjunction with the accompanying figures showing illustrativeembodiments of the invention, in which

[0016]FIG. 1 is a block diagram of an ultrasound therapy system having acollinear therapy ultrasound transducer and diagnostic imagingultrasound transducer;

[0017]FIG. 2 is a flow chart illustrating a method of operating thesystem of FIG. 1 to aim a therapy transducer to a targeted region; and

[0018]FIG. 3 is a flow chart illustrating a method of monitoring theapplication of ultrasound therapy by detecting both transient andpermanent changes in a region undergoing ultrasound therapy.

[0019] Throughout the figures, the same reference numerals andcharacters, unless otherwise stated, are used to denote like features,elements, components or portions of the illustrated embodiments.Moreover, while the subject invention will now be described in detailwith reference to the figures, it is done so in connection with theillustrative embodiments. It is intended that changes and modificationscan be made to the described embodiments without departing from the truescope and spirit of the subject invention as defined by the appendedclaims.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0020] The systems and methods described herein advantageously usesignal processing techniques to enhance the detection of non-linearproperties of regions undergoing ultrasound diagnostics or therapy. Theterm non-linearity imaging is used to broadly refer such techniques,which include, without limitation, harmonic imaging and pulse inversionimaging and the like. Throughout the disclosure, embodiments aredescribed in the context of harmonic imaging. However, this is onlyintended to be one exemplary manner of performing non-linearity imaging.

[0021]FIG. 1 is a simplified block diagram of the present ultrasounddiagnostic and therapy system. The system includes a therapy ultrasoundtransducer 102 for generating a therapy beam 104 which is focused to anapex referred to as the therapy beam focal point 106. The therapy beam104 is generally a high-intensity focused ultrasound (HIFU) beam. Thesystem also includes a diagnostic ultrasound transducer or array 108which can scan a region 108 with an ultrasound signal suitable for imageacquisition. Scanning of this type is known and can be performed byphysically directing the position of a transducer or by altering thepropagation characteristics of the array 108. Preferably, the diagnosticultrasound transducer 108 is arranged in a collinear manner with respectto the therapy ultrasound transducer 102. It is possible for thediagnostic ultrasound transducer 108 to be a receive only device. Insuch a case, the diagnostic ultrasound transducer would receive andprocess harmonic echo signals resulting from the incident signal fromthe therapy ultrasound transducer.

[0022] The transducers are coupled to appropriate ultrasoundgenerators/receivers 112, 114 respectively, which are operativelycoupled to a system controller 116. The system controller is alsocoupled to a display unit 118. These system components are well known inthe art of ultrasound imaging and therapy. A General Electric Logiq 700MR ultrasound unit which provides conventional B-mode (brightness mode)images and harmonic ultrasound images is suitable for practicing thepresent invention.

[0023]FIG. 2 is a flow chart illustrating a process for aiming thesystem of FIG. 1 prior to application of therapeutic ultrasound from thetherapy ultrasound transducer 102. First, with the therapy ultrasoundtransducer 102 inactive, a cross section image scan is obtained usingthe diagnostic ultrasound transducer 108 (step 205). This image scandata is stored (step 210). The image scan data can be stored as acquiredecho data, post-processed image data (pixels) or some intermediate dataform. Next, the therapy ultrasound transducer 102 is activated togenerate a brief pulse of ultrasound with a large peak-pressure while asignal from the diagnostic ultrasound transducer is also applied toacquire a second image data scan (step 215). The second image data scanis a non-linear imaging scan, such as harmonic imaging. The pulse fromthe therapy ultrasound transducer 102 is short enough such that notherapeutic tissue alteration results, such as heating or necrosis.

[0024] The ultrasound excitation from the therapy ultrasound transducer102 enhances the non-linear phenomena in the tissue and when the signalsfrom the therapy ultrasound transducer 102 and diagnostic transducercombine, this results in the generation of enhanced mixing products aswell as second, and higher order, harmonics. If, for example, thediagnostic transducer is operating in a frequency band centered about f1and the therapy transducer is operating in a band centered about f2, thenon-linearities induced in the tissue would result in mixing productsf1+f2, f1−f2 as well as harmonic components n*f1 and n*f2, where n is aninteger greater than 1. This results from the compression of tissueduring the high-pressure portions of the cycle and tissue relaxationduring the low pressure cycles of the therapy ultrasound signal whichalter the propagation properties of the tissue. These effects varydepending on the peak pressure value applied. Thus, the first image andsecond image will differ in regions that experience simultaneouspresence of the therapy beam and diagnostic beam, whose pressures arecoherently additive.

[0025] During acquisition of the second image scan, the therapyultrasound signal and the diagnostic ultrasound signal are temporallycoexistent. Generally, the therapy pulse is lower in frequency than thediagnostic pulse. Therefore, the coexistence can occur by superimposingthe high frequency diagnostic pulse on a portion of the lower frequencytherapy ultrasound pulse. Preferably, the high frequency diagnosticsignal is phase-synchronous with the diagnostic therapy signal such thatimaging takes place at defined portions of the therapy ultrasoundsignal. As the diagnostic ultrasound signal is scanned across the regionwhere the therapy ultrasound signal is present, the harmonic image willdetect the areas where the signals coincide. Alternatively, thediagnostic ultrasound transducer can take the form of a receive onlytransducer which is scanned across the region to detect harmoniccomponents of the therapy ultrasound signal only.

[0026] The difference between the first image scan and second image scancan be determined by subtracting the two image scans (step 220). Thedifference image data can be digitally enhanced by the controller 116using conventional digital signal processing techniques and thensuperimposed on the first image to indicate the position of the therapyultrasound signal 104 and focal point 106 (step 225). If the therapybeam is not in the desired position, the system can be re-aimed and theprocess can be repeated from step 205. Once the therapy ultrasoundsignal 104 is properly aimed, the therapy ultrasound signal 104 can beapplied for longer durations to induce necrosis of the targeted region.

[0027] In some cases, the resulting non-linearities from thecoincidental diagnostic ultrasound signal and therapy ultrasound signalwill be sufficiently pronounced such that the region occupied by thetherapy ultrasound signal 104 will be apparent in the image data scanacquired when the two signals are so applied. In this case, the methodof aiming the therapy ultrasound transducer can be performed in a singlestep of simultaneously operating the diagnostic ultrasound transducer108 and therapy ultrasound transducer 102 and viewing the resultingnon-linearity image.

[0028] The system of FIG. 1 can also be used to monitor the progress ofinduced tissue alteration resulting from the application of the therapyultrasound beam 104 by detecting changes in the degree of non-linearityin the tissue, referred to herein as the B/A coefficient ornon-linearity coefficient. Under the influence of the therapy ultrasoundbeam, transient changes in the non-linear properties of the tissue ariseas a result of in-situ temperature changes, and permanent changes in thenon-linear properties of the tissue arise from changes in the tissuemicrostructure. The in-situ temperature changes are transitory, with thetemperature returning to pre-exposure levels as the tissue coolsfollowing therapy exposure. Permanent changes in the tissuemicrostructure result from cell necrosis or other effects, such ascavitation, which result from application of the HIFU beam. Thus,measurement of transient changes can indicate both the degree andspatial extent of induced heating and measurements of permanent changesare indicative of the degree and extent of thermal lesions.

[0029]FIG. 3 is a flow chart illustrating a method of determiningin-situ heating and tissue alteration using progressive imageevaluation. Optionally, the process of aiming the therapy beam set forthin FIG. 2 can be applied to locate the therapy beam 104 (step 305). Thetherapy ultrasound beam 104 is then activated and baseline image scandata (I1) is acquired using the diagnostic ultrasound array 108 (step310). Therapy is continued for a time interval (T1) (step 315) andsecond image scan data (I2) is then acquired (step 320). The therapytransducer 102 can be deactivated for a second time interval (T2) (step325). The purpose of the second time interval (T2) is to allow thetemporary in-situ heating effect to dissipate. This period will varydepending on the power of the applied therapy ultrasound, the durationof the therapy, the nature of the tissue and the depth of the area beingtreated, among other variables. However, a time period of about 5-10seconds for T2 is considered reasonable to allow sufficient coolingunder various conditions. A third image scan data is then acquired (I3)at the end of the second time interval (step 330). Preferably, toenhance the non-linear effect in the tissue, if the first and secondimages were acquired with the therapy ultrasound present, the diagnostictransducer is activated along with a brief excitation from the highpressure therapy transducer 102 during acquisition of the third imagedata.

[0030] The aggregate induced effect from the application of the therapyultrasound signal is apparent from the difference between the secondimage scan data and the first image scan data (I2−I1) (step 335). Fromthe difference between the third image and the second image (I3−I2),transient effects due to heating can be determined (step 340). From thedifference between the third image and the first image (I3−I1),permanent changes due to alterations in the tissue microstructure can bedetermined (step 345). Once the transient changes and permanent changesare determined, the decision of whether to initiate another therapy beamsession is made (step 350), and control reverts to step 310 to continueor to step 355 to end therapy. If the decision is to continue, theapplication of the therapy ultrasound can be adjusted, if necessary, toalter the in-situ heating detected via the transient changes.

[0031] In determining the differences in the image scan data sets, thedata can be compared and processed in various forms. The data can becompared as raw echo data, as processed image data (pixels) or someintermediate data processing step.

[0032] In the image acquisition operations with respect to FIG. 3, theimage acquisition preferably takes place during a intervals when thetherapy ultrasound beam is being applied. This is preferred because ofthe enhanced non-linear effects of having the contemporaneousapplication of the diagnostic ultrasound and therapy ultrasound signalsenhance image acquisition. However, each of the images (I1, I2, I3) canalso be acquired with the therapy transducer turned off. In this case,harmonic imaging can still be performed, but with somewhat reducedefficacy.

[0033] In the method of FIG. 3, the B/A effects in lesions are measureddirectly. However, the present systems and methods can also be appliedto measure lesions indirectly by using harmonic imaging to evaluate“shadowing” that results from such lesions. Shadowing is a decrease inultrasound echo strength which causes a concomitant darkening incross-section ultrasound images. Shadowing results from a relativelyhigh attenuation coefficient in a region of tissue being subjected toultrasound. The incident ultrasound wave is attenuated when it passesthrough this region and the reflected wave is again attenuated as theecho signal returns to the transducer. Thus, the echo signal from distalsites behind the tissue causing the shadow is significantly reduced. Ingeneral, tissue attenuation coefficients increase with increasingfrequency. This not only reduces the intensity of the reflected echosignal, but also reduces the non-linear phenomenon discussed abovebecause the incident pressure of the ultrasound signal is also reduced.Therefore, shadows will be more pronounced when viewed with harmonicimages formed using high frequency harmonic components of the ultrasoundsignal.

[0034] The use of HIFU beam therapy can result in thermal lesions.Thermal lesions have an attenuation coefficient which is higher thanthat of normal tissue. Therefore, shadowing will result from thesethermal legions which can be enhanced by the use of harmonic imaging.Further, because shadowing will be manifest behind a lesion but not infront of the lesion, when non-linear imaging is employed, the shadowwill generally appear to originate from within the lesion and the lesionlocation can be readily identified. Thus, by using the diagnosticultrasound transducer 108 to capture progressive images of a regionundergoing therapy ultrasound, and evaluating these images for theoccurrence of shadows, the formation of lesions during this process canbe readily observed.

[0035] The present systems and methods provide a way of effectivelyaiming a therapy ultrasound transducer to insure that the HIFU beam isproperly directed to a targeted area. In addition, once properly aimed,the present systems and methods also provide an effective tool formonitoring the effects of the application of the HIFU beam duringtherapy.

[0036] Although the present invention has been described in connectionwith specific exemplary embodiments, it should be understood thatvarious changes, substitutions and alterations can be made to thedisclosed embodiments without departing from the spirit and scope of theinvention as set forth in the appended claims.

What is claimed is:
 1. A method for ultrasonic imaging comprising:acquiring a non-linearity imaging scan in a region including a targetfor application of an ultrasonic therapy beam, said acquiring takingplace in the presence of the ultrasonic therapy beam; and displaying theacquired non-linearity imaging scan.
 2. The method of claim 1, whereinthe non-linearity imaging scan is a harmonic imaging scan.
 3. The methodof claim 1, wherein the non-linearity imaging scan acquires thereflected harmonic components of the ultrasonic therapy beam.
 4. Amethod of monitoring the application of a focused ultrasonic therapybeam comprising: acquiring a first image scan using a first frequencyultrasound signal; acquiring a second image scan using the firstfrequency ultrasound signal in the presence of a therapy beam ultrasoundsignal; and determining difference properties in the first and secondimages descriptive of the therapy ultrasound signal.
 5. The method ofmonitoring the application of a therapy beam of claim 4, furthercomprising: generating a difference image from the first image scan andsecond image scan; and superimposing the difference image on the firstimage scan.
 6. The method of monitoring the application of a therapybeam of claim 4, wherein the second image scan is a non-linearityimaging scan.
 7. The method of monitoring the application of a therapybeam of claim 6, wherein the non-linearity imaging scan is a harmonicimaging scan.
 8. The method of monitoring the application of a therapybeam of claim 6, wherein the non-linearity imaging scan is a pulseinversion imaging scan.
 9. The method of monitoring the application of atherapy beam of claim 5, including the step of digitally enhancing thedifference image between said generating and superimposing operations.10. The method of monitoring the application of a therapy beam of claim4, wherein the difference properties are detected by evaluating mixingproducts of the first frequency ultrasound signal and the therapy beamultrasound signal.
 11. The method of monitoring the application of atherapy beam of claim 4, wherein the difference properties are detectedby evaluating harmonic components of the first frequency ultrasoundsignal.
 12. The method of monitoring the application of a therapy beamof claim 4, wherein the difference properties are detected by evaluatingharmonic components of the therapy ultrasound signal.
 13. A method ofoperating an ultrasound therapy system having a therapy ultrasoundtransducer and a diagnostic ultrasound transducer, comprising: operatingthe diagnostic ultrasound transducer for a first interval to acquirefirst ultrasound image scan data; operating the diagnostic ultrasoundtransducer and therapy ultrasound transducer for a second interval toacquire second ultrasound image scan data; and determining a differencein the first and second image scan data descriptive of the therapyultrasound transducer signal.
 14. The method of operating an ultrasoundtherapy system of claim 13, further comprising: generating a differenceimage from the first ultrasound image and second ultrasound image scandata; and superimposing the difference image on the first image scandata.
 15. The method of operating an ultrasound therapy system of claim14, further comprising digitally enhancing the difference image betweensaid generating and superimposing operations.
 16. The method ofoperating an ultrasound therapy system of claim 13, wherein thedifference in the image scan data is detected by evaluating mixingproducts of the diagnostic ultrasound signal and the therapy beamultrasound signal.
 17. The method of operating an ultrasound therapysystem of claim 13, wherein the difference in the image scan data aredetected by evaluating harmonic components of the diagnostic ultrasoundsignal.
 18. The method of operating an ultrasound therapy system ofclaim 13, wherein the difference in the image scan data are detected byevaluating harmonic components of the therapy beam ultrasound signal.19. The method of operating an ultrasound therapy system of claim 13,wherein the second image scan is a non-linearity imaging scan.
 20. Themethod of operating an ultrasound therapy system of claim 19, whereinthe non-linearity imaging scan is a harmonic imaging scan.
 21. Themethod of operating an ultrasound therapy system of claim 19, whereinthe non-linearity imaging scan is a pulse inversion imaging scan.
 22. Amethod of monitoring ultrasound therapy comprising: acquiring a firstnon-linearity image scan of a region; applying high intensity ultrasoundto a region for a first time period; acquiring a second non-linearityimage scan of the region; determining differences in the first andsecond non-linearity image scans to evaluate an induced effect in theregion.
 23. The method of monitoring an ultrasound therapy system ofclaim 22, further comprising: discontinuing the high intensityultrasound for a second time period; acquiring a third non-linearityimaging scan; determining transient changes in the region based on thethird and second scans; and determining permanent changes in the regionbased on the third and first scans.
 24. The method of monitoring anultrasound therapy system of claim 22, wherein the first non-linearityimaging scan is acquired while the high intensity ultrasound beingapplied.
 25. The method of monitoring an ultrasound therapy system ofclaim 22, wherein the second non-linearity imaging scan is acquiredwhile the high intensity ultrasound being applied.
 26. The method ofmonitoring an ultrasound therapy system of claim 22, wherein each of thefirst and second non-linearity imaging scans are acquired without thehigh intensity ultrasound being applied.
 27. A method of operating anultrasound therapy system having a therapy ultrasound transducer and adiagnostic ultrasound transducer, comprising: applying a first frequencysignal to a region from the therapy ultrasound transducer for a firstinterval; operating the diagnostic ultrasound transducer to acquireharmonic signals of the first frequency from the region; generating anultrasound image from the acquired harmonic signals.
 28. A method ofmonitoring ultrasound therapy comprising: acquiring a first ultrasoundimage scan of the region; applying high intensity ultrasound to a regionfor a first time period; acquiring a second ultrasound image scan of theregion; discontinuing the high intensity ultrasound for a second timeperiod; acquiring a third ultrasound image scan; determining transientnon-linearity changes in the region; and determining permanentnon-linearity changes in the region.
 29. The method of monitoringultrasound therapy of claim 28 further comprising determining aggregateinduced changes in the region by evaluating differences in the secondand the first ultrasound image scans.
 30. The method of monitoringultrasound therapy of claim 28 wherein said first, second and thirdimage scans are non-linearity imaging scans acquired in the presence ofthe high intensity ultrasound.
 31. The method of monitoring ultrasoundtherapy of claim 30 wherein the non-linearity imaging scans are harmonicimaging scans.
 32. The method of monitoring ultrasound therapy of claim28, wherein said first time period is selected to effect a therapeuticresult from the high intensity ultrasound.
 33. The method of monitoringultrasound therapy of claim 28, wherein said second time period isselected to allow in-situ cooling of the region subjected to the highintensity ultrasound.
 34. The method of monitoring ultrasound therapy ofclaim 28, wherein the transient changes are determined by subtractingone of the second image scan and third image scan from the other of thesecond image scan and third image scan.
 35. The method of monitoringultrasound therapy of claim 28, wherein the permanent changes aredetermined by subtracting one of the first image scan and third imagescan from the other of the first image scan and third image scan.